We have recently shown that: (1) beta-endorphin is biosynthesized in beef pituitary glands (PNAS 74:1403, 1977) (2) The intermediate lobe secretes almost exclusively LPH's peptides (PNAS 74:4276, 1977 and PNAS In Press). (3) The rat pars intermedia is a better system to study the maturation of the proopiocortin than the beef. Pulse-chase experiments clearly show that proopiocortin is transformed intracellularly into beta-LPH and beta-endorphin but not into Met-enkephalin (PNAS, submitted for publication). (4) The rat pars intermedia does not seem to produce any Leu-5-beta-endorphin. Thus we have completed the development of the best model system to study the ACTH beta-MSH-beta-endorphin common precursor. Not only will we be able to look at the amino acid sequence of the N-terminal portion of this precursor (in collaboration with Dr Herbert's group), but also to determine the exact position of ACTH and LPH (how many residues between them). Our system is not only very specific and identifies chemically the biosynthetic products but it provides us with a tool to study the biosynthesis of beta-endorphin in the brain and other tissues, a question of the utmost importance. We will purify and characterize the 31K common precursor to ACTH-beta-MSH and beta-endorphin. Our apprach will be through complete purification of the precursor from tissue and its chemical characterization as well as looking at the biosynthetic processes. We hope that such a combined approach shall lead to rapid and good understanding of this exciting model which might help to understand better the biological role of endorphins; we believe this model contains many elements which might eventually help to determine the physiological as well as the physiopathological relationship of ACTH and endorphins in health and disease, in the pituitary and in the brain.